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Pathway Description
De Novo Triacylglycerol Biosynthesis
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-01-22
Last Updated: 2019-10-24
A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. De novo biosynthesis of triglycerides is also known as the phosphatidic acid pathway, and it is mainly associated with the liver and adipose tissue. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). The next three steps are localized to the endoplasmic reticulum membrane. The enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. Next, magnesium-dependent phosphatidate phosphatase catalyzes the conversion of phosphatidic acid into diacylglycerol. Last, the enzyme diacylglycerol O-acyltransferase synthesizes triacylglycerol from diacylglycerol and a fatty acyl-CoA.
References
De Novo Triacylglycerol Biosynthesis References
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Pubmed: 8944226
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Pubmed: 16141072
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Pubmed: 9789033
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Pubmed: 15489334
Agarwal AK, Arioglu E, De Almeida S, Akkoc N, Taylor SI, Bowcock AM, Barnes RI, Garg A: AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34. Nat Genet. 2002 May;31(1):21-3. doi: 10.1038/ng880. Epub 2002 Apr 22.
Pubmed: 11967537
Lu B, Jiang YJ, Zhou Y, Xu FY, Hatch GM, Choy PC: Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARalpha in murine heart. Biochem J. 2005 Jan 15;385(Pt 2):469-77. doi: 10.1042/BJ20041348.
Pubmed: 15367102
Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001.
Pubmed: 21183079
Dobson DE, Groves DL, Spiegelman BM: Nucleotide sequence and hormonal regulation of mouse glycerophosphate dehydrogenase mRNA during adipocyte and muscle cell differentiation. J Biol Chem. 1987 Feb 5;262(4):1804-9.
Pubmed: 3027100
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Pubmed: 3755721
Phillips M, Djian P, Green H: The nucleotide sequence of three genes participating in the adipose differentiation of 3T3 cells. J Biol Chem. 1986 Aug 15;261(23):10821-7.
Pubmed: 3015943
Huffman TA, Mothe-Satney I, Lawrence JC Jr: Insulin-stimulated phosphorylation of lipin mediated by the mammalian target of rapamycin. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):1047-52. doi: 10.1073/pnas.022634399. Epub 2002 Jan 15.
Pubmed: 11792863
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Pubmed: 11138012
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0015896
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